Specific delivery of drugs and pharmaceutical compositions to the colon is important in the treatment of a wide variety of diseases and conditions. Colon diseases include such conditions such as Crohn's disease, colitis (particularly ulcerative colitis), irritable bowel syndrome and the like. These diseases include a spectrum of inflammatory bowel disorders with overlapping clinical, epidemiologic and pathologic findings but without a definite etiology. Both Crohn's disease and ulcerative colitis are characterized by chronic inflammation at various sites of the GI tract, generally the colon (i.e., that part of the intestine from the cecum to the rectum). Crohn's disease seems to affect the cecum primarily while ulcerative colitis seems to go past the second turn in the colon and affect the splenic flexure.
Targeting of drugs to the colon provides the ability to locally treat large bowel diseases, thus avoiding or decreasing systemic effects of drugs or inconvenient and painful transcolonic administration of drugs. Furthermore, there is an increased need for delivery to the colon of drugs that are reported to be absorbable in the colon, such as steroids, which would increase the efficiency of the treatment and enable the reduction in the required effective dose. Godbillon, J., et al., Br. J. Clin. Pharmacol. 19:113S (1985); Antonin, K. H. et al., Br. J. Clin. Pharmacal. 19:137S (1985); Fara, J. W., 3rd International Conference on Drug Absorption, Edinburgh (1988); for a review see Rubinstein, A., Biopharm. Drug Dispos. 11:465-475 (1990).
There have been previous attempts to provide oral controlled release delivery systems capable of passing over the entire tract of the small intestine, including the duodenum, jejunum, and ileum, so that the active ingredients can be released directly in the colon, if such site specific delivery is desired. However, the targeting of drugs to desired locations in the alimentary canal can be complicated. Because of its location at the distal portion of the alimentary canal, the colon is particularly difficult to access. The design of orally administered colonic delivery systems must take into account factors such as the pH of the alimentary canal and the presence of enzymes in the stomach and small intestine. The high acidity of the gastric tract and presence of proteolytic and other enzymes therein generates a highly digestive environment that readily disintegrates pharmaceutical formulations that do not possess some type of gastro-resistance protection. This disintegration would typically have a detrimental effect upon the delayed release of the active agent.
PCT publications WO 02/072033 and WO 02/072034, the disclosures of which are hereby incorporated by reference, disclose chronotherapeutic pharmaceutical formulations comprising a core containing an active agent (e.g., a drug) and a delayed release compression coating comprising a natural or synthetic gum applied onto the surface of the core.
It is considered desirable by those skilled in the art to provide an oral controlled release delivery system that is adaptable to delay the release of a drug(s) such that the drug is delivered to the colon of a human.